Many treatments would benefit from a zero-order release rate, potentially improving efficacy and reducing side effects. Furthermore, a long-term, implantable device may reduce the number of unpleasant injections and improve compliance.
Because their pores are so similar in size to the molecules they deliver, nanoporous membranes have shown the ability to confine molecular diffusion, leading to a constant rate, non-Fickian drug release. However, most nanoporous membranes are made of silicon or alumina and attached to a reservoir using an adhesive; none of these materials are commonly used as a tissue-contacting surface in FDA-approved implantable devices.
In contrast, titanium and titanium oxide (titania) have been used for decades with an excellent record of biocompatibility. The manufacture of an all-titanium/titania membrane has been previously reported, including demonstration of zero-order diffusion in vitro, an expected in vivo pharmacokinetic profile, and data showing biocompatibility for over a year. What is needed, however, is a method for preparing nanopores where the internal diameter can be precisely controlled such that zero-order release can be achieved for any therapeutic agent. Surprisingly, the present invention meets this and other needs.